AMG 595 First-in-Human in Recurrent Gliomas

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01475006
• Other study ID #: 20090505
• Status: Completed
• Phase: Phase 1
• First received: September 29, 2011
• Last updated: April 14, 2016
• Start date: February 2012
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Royal Adelaide Hospital Research Ethics CommitteeAustralia:Melbourne Health Office for ResearchUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is an open-label, sequential dose exploration study of single agent AMG 595 administered in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA). The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of AMG 595, and also to evaluate the objective response rate in subjects receiving AMG 595. This study will be conducted in two parts. Part 1 will explore doses of AMG 595 in subjects with recurrent GBM and/or AA. Part 2 (dose expansion) will examine the MTD established in Part 1 in subjects with recurrent GBM.

Description:

This study of AMG 595 will be conducted in two parts: Part 1 (dose exploration) and Part 2 (dose expansion). Part 1 of the study is in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA), and Part 2 is examining the MTD in subjects with recurrent GBM. Approximately 30-40 subjects may be enrolled in Part 1, and up to 36 subjects may be enrolled in Part 2. The dose of AMG 595 utilized in Part 2 will be dependent upon data obtained in Part 1 of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Karnofsky performance score > or = 70%

• Must have pathologically documented, and definitively diagnosed recurrent WHO Grade IV advanced malignant glioblastoma multiforme (Part 1 and Part 2) and/or WHO Grade III anaplastic astrocytoma (Part 1 only).

• GBM and/or AA tumors expressing EGFRvIII as assessed on archived tissue by IHC staining of sections containing a minimum of 100 evaluable tumor cells.

• Archived tumor tissue from the initial diagnosis or subsequent relapse(s) of Grade IV advanced malignant glioblastoma multiforme or Grade III anaplastic astrocytoma available for submission to central review.

• Subjects with recurrent disease (confirmed by MRI and evaluable by Macdonald criteria) at the time of first or second recurrence or progression following initial definitive therapy(s)

• QTcF = 470 msec

• Hematological function, as follows: Absolute neutrophil count (ANC) = 1.5 x 10^9/L, Platelet count = 100 x 10^9/L, Hemoglobin > 9 g/dL

• Renal function, as follows: Estimated glomerular filtration rate using the Modified Diet in Renal Disease (MDRD) equation > 45 mL/min/1.73m^2, Urinary protein quantitative value of < 30 mg/dL in urinalysis or = 1+ on dipstick, unless quantitative protein is < 500 mg in a 24 hr urine sample

Exclusion Criteria:

• History of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment.

• Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage.

• Peripheral sensory neuropathy > Grade 2.

• Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome.

• Recent infection requiring intravenous anti-infective treatment that was completed = 14 days before enrollment.

• Received radiation therapy within 12 weeks before enrollment or has not recovered from the toxic effects of such therapy.

• For Part 1 (dose escalation): Treatment with bevacizumab or antiangiogenic therapy within 4 weeks before enrollment, or for Part 2 (dose expansion): any prior treatment with bevacizumab or antiangiogenic therapy.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Malignant Glioma
• Anaplastic Astrocytomas
• Astrocytoma
• Glioblastoma
• Glioblastoma Multiforme
• Glioma

Intervention

Drug:
• AMG 595
AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

Locations

Country	Name	City	State
Australia	Research Site	Parkville	Victoria
United States	Research Site	Boston	Massachusetts
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs		28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available)	Yes
Primary	PK Parameters: Cmax, Cmin, and if feasible half life - 8 time points up to 6 weeks		28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available)	Yes
Primary	Objective response in GBM tumors as assessed by Macdonald criteria		3 years	No
Primary	Dose limiting toxicity used to estimate the MTD		28 Days after last subject enrolled of each cohort in Part 1 and every 10, 20 and 30 subject enrolled in part 2 (if available)	Yes
Secondary	Clinical benefit rate		every 6 months	No
Secondary	Progressive free survival		3 years	No
Secondary	Overall survival		3 years	No
Secondary	Anti-AMG 595 antibody formation		3 years	No

External Links

•   AmgenTrials clinical trials website